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[68Ga]Ga-FAPI-04 PET/CT in the evaluation of epithelial ovarian cancer: comparison with [18F]F-FDG PET/CT

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

To compare the efficacy of [68Ga]Ga-FAPI-04 PET/CT in primary or recurrent tumors and metastatic lesions of epithelial ovarian cancer (EOC) with that of fluorine-18 fluorodeoxyglucose ([18F]F-FDG) PET/CT.

Methods

Forty-nine patients (median age, 57 years; IQR, 51–66 years) with histologically proven primary or relapsed EOC were enrolled. Participants underwent [18F]F-FDG and [68Ga]Ga-FAPI-04 PET/CT. The detection rate, diagnostic accuracy, semiquantitative parameters, tumor staging, and clinical management of the tracers were compared. The diagnostic performance of [18F]F-FDG and [68Ga]Ga-FAPI-04 PET/CT was evaluated and compared using surgical pathology. Differences between methods regarding the peritoneal cancer index (PCI) using preoperative imaging, surgical PCI, and tumor markers (CA125, HE4) were also assessed regarding peritoneal metastases.

Results

Among the 49 patients, 28 had primary EOC; 21 had relapsed EOC. [68Ga]Ga-FAPI-04 PET/CT outperformed [18F]F-FDG PET/CT in detecting peritoneal metastases (96.8% vs. 83.0%; p < 0.001), retroperitoneal (99.5% vs. 91.4%; p < 0.001), and supradiaphragmatic lymph node metastases (100% vs. 80.4%; p < 0.001). Compared with [18F]F-FDG, [68Ga]Ga-FAPI-04 showed higher SUVmax for peritoneal metastases (17.31 vs. 13.68; p = 0.026) and retroperitoneal (8.72 vs. 6.56; p < 0.001) and supradiaphragmatic lymph node metastases (6.39 vs. 4.20; p < 0.001). Moreover, [68Ga]Ga-FAPI-04 PET/CT showed higher sensitivity compared with [18F]F-FDG PET/CT for detecting metastatic lymph nodes (80.6% vs. 61.3%; p = 0.031) and peritoneal metastases (97.5% vs. 75.9%; p < 0.001), using surgical pathology as the gold standard. Compared with [18F]F-FDG PET/CT, [68Ga]Ga-FAPI-04 PET/CT led to an upgrade in 14.3% and 33.3% of treatment-naive and relapse participants, resulting in management changes in 10.7% and 19.0% of the patients, respectively. The median PCIFAPI scores were significantly higher than PCIFDG (15 vs. 11; p < 0.001) and positively correlated with CA125 and HE4 levels and surgical PCI.

Conclusion

[68Ga]Ga-FAPI-04 PET/CT achieved higher sensitivity than [18F]F-FDG PET/CT in the detection and diagnosis of lymph node and peritoneal metastases, suggesting advantages regarding the preoperative staging of patients with EOC and, thereby, improving treatment decision-making.

Trial registration

NCT05034146. Registered February 23, 2021

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Data availability

Data generated or analyzed during the study are available from the corresponding author by request.

References

  1. Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73:17–48. https://doi.org/10.3322/caac.21763.

    Article  PubMed  Google Scholar 

  2. Momenimovahed Z, Tiznobaik A, Taheri S, Salehiniya H. Ovarian cancer in the world: epidemiology and risk factors. Int J Womens Health. 2019;11:287–99. https://doi.org/10.2147/IJWH.S197604.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Llueca A, Serra A, Rivadulla I, Gomez L, Escrig J. MUAPOS working group (Multidisciplinary Unit of Abdominal Pelvic Oncology Surgery). Prediction of suboptimal cytoreductive surgery in patients with advanced ovarian cancer based on preoperative and intraoperative determination of the peritoneal carcinomatosis index. World J Surg Oncol. 2018;16:37. https://doi.org/10.1186/s12957-018-1339-0.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Lengyel E. Ovarian cancer development and metastasis. Am J Pathol. 2010;177:1053–64. https://doi.org/10.2353/ajpath.2010.100105.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Keunecke C, Kulbe H, Dreher F, Taube ET, Chekerov R, Horst D, et al. Predictive biomarker for surgical outcome in patients with advanced primary high-grade serous ovarian cancer. Are we there yet? An analysis of the prospective biobank for ovarian cancer. Gynecol Oncol. 2022;166:334–43. https://doi.org/10.1016/j.ygyno.2022.06.010.

    Article  CAS  PubMed  Google Scholar 

  6. Bharwani N, Reznek RH, Rockall AG. Ovarian Cancer Management: the role of imaging and diagnostic challenges. Eur J Radiol. 2011;78:41–51. https://doi.org/10.1016/j.ejrad.2010.11.039.

    Article  PubMed  Google Scholar 

  7. Nougaret S, Tardieu M, Vargas HA, Reinhold C, Vande Perre S, Bonanno N, et al. Ovarian cancer: An update on imaging in the era of radiomics. Diagn Interv Imaging. 2019;100:647–55. https://doi.org/10.1016/j.diii.2018.11.007.

    Article  CAS  PubMed  Google Scholar 

  8. Forstner R, Sala E, Kinkel K, Spencer JA; European Society of Urogenital Radiology. ESUR guidelines: ovarian cancer staging and follow-up. Eur Radiol. 2010; 20:2773-2780. https://doi.org/10.1007/s00330-010-1886-4.

  9. Tempany CM, Zou KH, Silverman SG, Brown DL, Kurtz AB, McNeil BJ. Staging of advanced ovarian cancer: comparison of imaging modalities--report from the Radiological Diagnostic Oncology Group. Radiol. 2000;215:761–7. https://doi.org/10.1148/radiology.215.3.r00jn25761.

    Article  CAS  Google Scholar 

  10. Delgado Bolton RC, Aide N, Colletti PM, Ferrero A, Paez D, Skanjeti A, et al. EANM guideline on the role of 2-[18F]FDG PET/CT in diagnosis, staging, prognostic value, therapy assessment and restaging of ovarian cancer, endorsed by the American College of Nuclear Medicine (ACNM), the Society of Nuclear Medicine and Molecular Imaging (SNMMI) and the International Atomic Energy Agency (IAEA). Eur J Nucl Med Mol Imaging. 2021;48:3286–302. https://doi.org/10.1007/s00259-021-05450-9.

    Article  PubMed  Google Scholar 

  11. Roze JF, Hoogendam JP, van de Wetering FT, Spijker R, Verleye L, Vlayen J, et al. Positron emission tomography (PET) and magnetic resonance imaging (MRI) for assessing tumour resectability in advanced epithelial ovarian/fallopian tube/primary peritoneal cancer. Cochrane Database Syst Rev. 2018;10:CD012567. https://doi.org/10.1002/14651858.CD012567.pub2.

    Article  PubMed  Google Scholar 

  12. Tanizaki Y, Kobayashi A, Shiro M, Ota N, Takano R, Mabuchi Y, et al. Diagnostic value of preoperative SUVmax on FDG-PET/CT for the detection of ovarian cancer. Int J Gynecol Cancer. 2014;24:454–60. https://doi.org/10.1097/IGC.0000000000000074.

    Article  PubMed  Google Scholar 

  13. Li C, Tian Y, Chen J, Jiang Y, Xue Z, Xing D, et al. Usefulness of [68Ga]FAPI-04 and [18F]FDG PET/CT for the detection of primary tumour and metastatic lesions in gastrointestinal carcinoma: a comparative study. Eur Radiol. 2023;33:2779–91. https://doi.org/10.1007/s00330-022-09251-y.

    Article  CAS  PubMed  Google Scholar 

  14. Giesel FL, Kratochwil C, Schlittenhardt J, Dendl K, Eiber M, Staudinger F, et al. Head-to-head intra-individual comparison of biodistribution and tumor uptake of 68Ga-FAPI and 18F-FDG PET/CT in cancer patients. Eur J Nucl Med Mol Imaging. 2021;48:4377–85. https://doi.org/10.1007/s00259-021-05307-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Dendl K, Koerber SA, Finck R, Mokoala KMG, Staudinger F, Schillings L, et al. 68Ga-FAPI-PET/CT in patients with various gynecological malignancies. Eur J Nucl Med Mol Imaging. 2021;48:4089–100. https://doi.org/10.1007/s00259-021-05378-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Zheng W, Liu L, Feng Y, Wang L, Chen Y. Comparison of 68Ga-FAPI-04 and fluorine-18-fluorodeoxyglucose PET/computed tomography in the detection of ovarian malignancies. Nucl Med Commun. 2023;44:194–203. https://doi.org/10.1097/MNM.0000000000001653.

    Article  CAS  PubMed  Google Scholar 

  17. Liu S, Feng Z, Xu X, Ge H, Ju X, Wu X, et al. Head-to-head comparison of [18F]-FDG and [68Ga]-DOTA-FAPI-04 PET/CT for radiological evaluation of platinum-sensitive recurrent ovarian cancer. Eur J Nucl Med Mol Imaging. 2023;50:1521–31. https://doi.org/10.1007/s00259-022-06096-x.

    Article  CAS  PubMed  Google Scholar 

  18. Ledermann JA, Raja FA, Fotopoulou C, Gonzalez-Martin A, Colombo N, Sessa C, ESMO Guidelines Working Group. Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24(Suppl 6):vi24–32. https://doi.org/10.1093/annonc/mdt333.

    Article  PubMed  Google Scholar 

  19. Sala E, Rockall AG, Freeman SJ, Mitchell DG, Reinhold C. The added role of MR imaging in treatment stratification of patients with gynecologic malignancies: what the radiologist needs to know. Radiol. 2013;266:717–40. https://doi.org/10.1148/radiol.12120315.

    Article  Google Scholar 

  20. Kim HW, Won KS, Zeon SK, Ahn BC, Gayed IW. Peritoneal carcinomatosis in patients with ovarian cancer: enhanced CT versus 18F-FDG PET/CT. Clin Nucl Med. 2013;38:93–7. https://doi.org/10.1097/RLU.0b013e31826390ec.

    Article  PubMed  Google Scholar 

  21. Prat J, FIGO Committee on Gynecologic Oncology. Staging classification for cancer of the ovary, fallopian tube, and peritoneum. Int J Gynaecol Obstet. 2014;124:1–5. https://doi.org/10.1016/j.ijgo.2013.10.001.

    Article  PubMed  Google Scholar 

  22. Yousefi M, Dehghani S, Nosrati R, Ghanei M, Salmaninejad A, Rajaie S, et al. Current insights into the metastasis of epithelial ovarian cancer-hopes and hurdles. Cell Oncol (Dordr). 2020;43:515–38. https://doi.org/10.1007/s13402-020-00513-9.

    Article  PubMed  Google Scholar 

  23. Mutch DG, Prat J. 2014 FIGO Staging for Ovarian, Fallopian Tube and Peritoneal Cancer. Gynecol. Oncol. 2014;133:401–4. https://doi.org/10.1016/j.ygyno.2014.04.013.

    Article  PubMed  Google Scholar 

  24. Armstrong DK, Alvarez RD, Backes FJ, Bakkum-Gamez JN, Barroilhet L, Behbakht K, et al. NCCN Guidelines® Insights: Ovarian Cancer, Version 3.2022. J Natl Compr Canc Netw. 2022;20:972–80. https://doi.org/10.6004/jnccn.2022.0047.

    Article  PubMed  Google Scholar 

  25. Lan L, Liu H, Wang Y, Deng J, Peng D, Feng Y, et al. The potential utility of [68Ga]Ga-DOTA-FAPI-04 as a novel broad-spectrum oncological and non-oncological imaging agent-comparison with [18F]FDG. Eur J Nucl Med Mol Imaging. 2022;49:963–79. https://doi.org/10.1007/s00259-021-05522-w.

    Article  CAS  PubMed  Google Scholar 

  26. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47. https://doi.org/10.1016/j.ejca.2008.10.026.

  27. Moro F, Bertoldo V, Avesani G, Moruzzi MC, Mascilini F, Bolomini G, et al. Fusion imaging in preoperative assessment of extent of disease in patients with advanced ovarian cancer: feasibility and agreement with laparoscopic findings. Ultrasound Obstet Gynecol. 2021;58:916–25. https://doi.org/10.1002/uog.23650.

    Article  CAS  PubMed  Google Scholar 

  28. Avesani G, Arshad M, Lu H, Fotopoulou C, Cannone F, Melotti R, et al. Radiological assessment of Peritoneal Cancer Index on preoperative CT in ovarian cancer is related to surgical outcome and survival. Radiol Med. 2020;125:770–6. https://doi.org/10.1007/s11547-020-01170-6.

    Article  PubMed  Google Scholar 

  29. Kyriazi S, Collins DJ, Morgan VA, Giles SL, deSouza NM. Diffusion-weighted imaging of peritoneal disease for noninvasive staging of advanced ovarian cancer. Radiographics. 2010;30:1269–85. https://doi.org/10.1148/rg.305105073.

    Article  PubMed  Google Scholar 

  30. de Bree E, Koops W, Kröger R, van Ruth S, Witkamp AJ, Zoetmulder FA. Peritoneal carcinomatosis from colorectal or appendiceal origin: correlation of preoperative CT with intraoperative findings and evaluation of interobserver agreement. J Surg Oncol. 2004;86:64–73. https://doi.org/10.1002/jso.20049.

    Article  PubMed  Google Scholar 

  31. Morland D, Jallerat P, Brixi H, Cadiot G, Papathanassiou D, Deguelte S. Performances of 18F-FDOPA PET/CT in the Preoperative Evaluation of the Peritoneal Cancer Index in Small Intestine Neuroendocrine Tumors. Clin Nucl Med. 2022;47:294–8. https://doi.org/10.1097/RLU.0000000000004057.

    Article  PubMed  Google Scholar 

  32. Pang Y, Zhao L, Luo Z, Hao B, Wu H, Lin Q, et al. Comparison of 68Ga-FAPI and 18F-FDG Uptake in Gastric, Duodenal, and Colorectal Cancers. Radiol. 2021;298:393–402. https://doi.org/10.1148/radiol.2020203275.

    Article  Google Scholar 

  33. Pandit-Taskar N, Schöder H, Gonen M, Larson SM, Yeung HW. Clinical significance of unexplained abnormal focal FDG uptake in the abdomen during whole-body PET. AJR Am J Roentgenol. 2004;183:1143–7. https://doi.org/10.2214/ajr.183.4.1831143.

    Article  PubMed  Google Scholar 

  34. Salminen L, Gidwani K, Grènman S, Carpén O, Hietanen S, Pettersson K, et al. HE4 in the evaluation of tumor load and prognostic stratification of high grade serous ovarian carcinoma. Acta Oncol. 2020;59:1461–8. https://doi.org/10.1080/0284186X.2020.1827157.

    Article  CAS  PubMed  Google Scholar 

  35. Davenport C, Rai N, Sharma P, Deeks JJ, Berhane S, Mallett S, et al. Menopausal status, ultrasound and biomarker tests in combination for the diagnosis of ovarian cancer in symptomatic women. Cochrane Database Syst Rev. 2022;7:CD011964. https://doi.org/10.1002/14651858.CD011964.pub2.

    Article  PubMed  Google Scholar 

  36. Pereira A, Magrina JF, Rey V, Cortes M, Magtibay PM. Pelvic and aortic lymph node metastasis in epithelial ovarian cancer. Gynecol Oncol. 2007;105:604–8. https://doi.org/10.1016/j.ygyno.2007.01.028.

    Article  PubMed  Google Scholar 

  37. Fang C, Zhang Y, Zhao L, Chen X, Xia L, Zhang P. The relationship between retroperitoneal lymphadenectomy and survival in advanced ovarian cancer patients. BMC Cancer. 2020;20:654. https://doi.org/10.1186/s12885-020-07144-1.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Fischerova D, Pinto P, Burgetova A, Masek M, Slama J, Kocian R, et al. Preoperative staging of ovarian cancer: comparison between ultrasound, CT and whole-body diffusion-weighted MRI (ISAAC study). Ultrasound Obstet Gynecol. 2022;59:248–62. https://doi.org/10.1002/uog.23654.

    Article  CAS  PubMed  Google Scholar 

  39. Mimoun C, Rouzier R, Benifla JL, Fauconnier A, Huchon C. Preoperative CT or PET/CT to Assess Pelvic and Para-Aortic Lymph Node Status in Epithelial Ovarian Cancer? A Systematic Review and Meta-Analysis. Diagnostics (Basel). 2021;11:1748. https://doi.org/10.3390/diagnostics11101748.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Laasik M, Kemppainen J, Auranen A, Hietanen S, Grénman S, Seppänen M, et al. Behavior of FDG-avid supradiaphragmatic lymph nodes in PET/CT throughout primary therapy in advanced serous epithelial ovarian cancer: a prospective study. Cancer Imaging. 2019;19:27. https://doi.org/10.1186/s40644-019-0215-7.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Nasser S, Kyrgiou M, Krell J, Haidopoulos D, Bristow R, Fotopoulou C. A Review of Thoracic and Mediastinal Cytoreductive Techniques in Advanced Ovarian Cancer: Extending the Boundaries. Ann Surg Oncol. 2017;24:3700–5. https://doi.org/10.1245/s10434-017-6051-8.

    Article  PubMed  Google Scholar 

  42. Polack M, Hagenaars SC, Couwenberg A, Kool W, Tollenaar RAEM, Vogel WV, et al. Characteristics of tumour stroma in regional lymph node metastases in colorectal cancer patients: a theoretical framework for future diagnostic imaging with FAPI PET/CT. Clin Transl Oncol. 2022;24:1776–84. https://doi.org/10.1007/s12094-022-02832-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

We appreciate Professor Sheng Li (Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan University) for his help in statistics analysis and Dr. Jane Charbonneau for the wording and grammatical corrections.

Funding

This work was supported by the Improvement Project for Theranostic Ability on Difficulty Miscellaneous Disease (tumor) (No. ZLYNXM202007) and the National Natural Science Foundation of China (No. 82171986).

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Author notes

  1. J. Chen and K. Xu contributed equally to this work.

Authors and Affiliations

  1. Department of Nuclear Medicine, Zhongnan Hospital of Wuhan University, No.169 Donghu Road, Wuhan, 430071, China

    Jie Chen, Kui Xu, Chongjiao Li, Yueli Tian, Ling Li, Bing Wen & Yong He

  2. Department of Gynecological Oncology, Zhongnan Hospital of Wuhan University, No.169 Donghu Road, Wuhan, 430071, China

    Can He & Hongbing Cai

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  1. Jie Chen
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Contributions

All authors contributed to the study conception and design. Yong He and Hongbing Cai designed the research. Jie Chen and Kui Xu conducted the literature search. Chongjiao Li, Yueli Tian, Ling Li, Bing Wen and Can He recruited the patients. Jie Chen, Kui Xu, Chongjiao Li and Ling Li conducted the study and collected and analyzed data. All authors read and approved the final manuscript.

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Correspondence to Hongbing Cai or Yong He.

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Chen, J., Xu, K., Li, C. et al. [68Ga]Ga-FAPI-04 PET/CT in the evaluation of epithelial ovarian cancer: comparison with [18F]F-FDG PET/CT. Eur J Nucl Med Mol Imaging 50, 4064–4076 (2023). https://doi.org/10.1007/s00259-023-06369-z

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